This invention relates generally to treatment of selected tissue by inter-vivo radiation, specifically to radiation treatment of traumatized regions of the cardiovascular system to prevent restenosis of the traumatized region, more specifically to radiation treatment to prevent restenosis of an artery traumatized by percutaneous transluminal angioplasty (PTA).
PTA treatment of the coronary arteries, percutaneous transluminal coronary angioplasty (PTCA), also known as balloon angioplasty, is the predominant treatment for coronary vessel stenosis. Approximately 300,000 procedures were performed in the United States (U.S.) in 1990 and an estimated 400,000 in 1992. The U.S. market constitutes roughly half of the total market for this procedure. The increasing popularity of the PTCA procedure is attributable to its relatively high success rate, and its minimal invasiveness compared with coronary by-pass surgery. Patients treated by PTCA, however, suffer from a high incidence of restenosis, with about 35% of all patients requiring repeat PTCA procedures or by-pass surgery, with attendant high cost and added patient risk. More recent attempts to prevent restenosis by use of drugs, mechanical devices, and other experimental procedures have had limited success.
Restenosis occurs as a result of injury to the arterial wall during the lumen opening angioplasty procedure. In some patients, the injury initiates a repair response that is characterized by hyperplastic growth of the vascular smooth muscle cells in the region traumatized by the angioplasty. The hyperplasia of smooth muscle cells narrows the lumen that was opened by the angioplasty, thereby necessitating a repeat PTCA or other procedure to alleviate the restenosis.
Preliminary studies indicate that intravascular radiotherapy (IRT) has promise in the prevention or long-term control of restenosis following angioplasty. It is also speculated that IRT may be used to prevent stenosis following cardiovascular graft procedures or other trauma to the vessel wall. Proper control of the radiation dosage, however, is critical to impair or arrest hyperplasia without causing excessive damage to healthy tissue. Overdosing of a section of blood vessel can cause arterial necrosis, inflammation and hemorrhaging. Underdosing will result in no inhibition of smooth muscle cell hyperplasia, or even exacerbation of the hyperplasia and resulting restenosis.
U.S. Pat. No. 5,059,166 to Fischell discloses an IRT method that relies on a radioactive stent that is permanently implanted in the blood vessel after completion of the lumen opening procedure. Close control of the radiation dose delivered to the patient by means of a permanently implanted stent is difficult to maintain because the dose is entirely determined by the activity of the stent at the particular time it is implanted. Additionally, the dose delivered to the blood vessel is non-uniform because the tissue that is in contact with the individual strands of the stent receive a higher dosage than the tissue between the individual strands. This non-uniform dose distribution is especially critical if the stent incorporates a low penetration source such as a beta emitter.
U.S. Pat. No. 5,302,168 to Hess teaches use of a radioactive source contained in a flexible carrier with remotely manipulated windows. H. Bottcher, et al. of the Johann Wolfgang Goerhe University Medical Center, Frankfurt, Germany report in November 1992 of having treated human superficial femoral arteries with a similar endoluminal radiation source. These methods generally require use of a higher activity source than the radioactive stent to deliver an effective dose. Accordingly, measures must be taken to ensure that the source is maintained reasonably near the center of the lumen to prevent localized overexposure of tissue to the radiation source. Use of these higher activity sources also dictates use of expensive shielding and other equipment for safe handling of the source.
The aforementioned application Ser. No. 08/352,318, incorporated herein by reference, discloses IRT methods and apparatus for delivering an easily controllable uniform dosage of radiation to the walls of the blood vessel without the need for special measures to center the radiation source in the lumen, the need for expensive shielding to protect medical personnel, or the need for expensive remote after loaders to handle the higher activity sources. This is accomplished by introducing a radioactive liquid into a balloon catheter to expand the balloon until it engages the blood vessel walls. The aforementioned application also discloses methods and apparatus for relieving the stenosed region of the blood vessel and performing the IRT procedure with a single apparatus, which may include an angioplasty balloon with a separately inflatable outer IRT balloon.
In certain applications, however, the size of the blood vessel is too small to admit a catheter with a profile large enough to accommodate separate inflation lumens for an outer and inner balloon. A smaller profile IRT catheter be obtained, however, by eliminating the IRT inflation lumen, thereby converting the outer IRT balloon to a containment membrane.
Where the blood vessel size permits, a further advantage may be obtained, if a combination angioplasty and IRT catheter includes means for extending the IRT treatment area beyond the angioplasty treatment area to irradiate a region extending proximal and distal of the angioplasty treatment area. By providing for IRT treatment that covers a wider area than the angioplasty treatment area, all of the tissue traumatized by the angioplasty is irradiated and IRT procedures. Accordingly, proper inhibition of smooth muscle cell hyperplasia is more reliably achieved.
According to the present invention, a single treatment catheter is used to perform all, or at least the final stage of, the angioplasty procedure and to perform the entire IRT procedure. In an embodiment of the present invention, the treatment catheter comprises a flexible elongate member having an angioplasty balloon that is surrounded by an IRT treatment balloon having a separate inflation lumen. The catheter is advanced through the cardiovascular system of the patient until the balloons are positioned at a target area comprising the stenosed region of the blood vessel. The stenosis is first relieved using the inner angioplasty balloon, then the target tissue is irradiated by filling the IRT treatment balloon with a radioactive liquid until until the outer wall of the balloon gently engages the inner wall of the blood vessel.
The radioactive fluid comprises a suspension of a beta emitting material such as 32P or a photon emitting material such as 125I in a liquid carrier. The radiation emitted by such sources is quickly absorbed by surrounding tissue and will not penetrate substantially beyond the walls of the blood vessel being treated. Accordingly, incidental irradiation of the heart and other organs adjacent to the treatment site is substantially eliminated. Because the radioactive liquid has a substantially uniform suspension of radioactive material, the radiation emitted at the surface of the balloon in contact with the target area of the blood vessel is inherently uniform. Accordingly, uniform irradiation of the blood vessel wall is also inherent.
According to an embodiment of the present invention, the outer IRT treatment balloon is made longer than the inner angioplasty balloon. Accordingly, when filled, the IRT treatment balloon will irradiate a section of the blood vessel that extends on both sides beyond the area treated with the angioplasty balloon. This extended IRT treatment area provides a margin of safety to ensure that, even if the catheter shifts slightly during the treatment, the entire traumatized region of the blood vessel will be treated to prevent smooth muscle cell hyperplasia.
The catheter of the present invention may also be equipped with perfusion ports proximal and distal of the balloon to permit blood flow past the balloon when inflated.
According to another embodiment of the present invention, a third balloon is provided that completely envelopes the IRT treatment balloon. This containment balloon acts as a containment vessel in the event the IRT treatment balloon ruptures when filled with the radioactive fluid. In use, prior to filling the treatment balloon with the radioactive fluid, the containment balloon is filled, preferably with a non-toxic radio-opaque fluid, to verify the integrity of the containment balloon. The radio-opaque fluid filled containment balloon may also be used to verify correct positioning of the catheter within the target area of the blood vessel.
After the angioplasty procedure is performed, the angioplasty balloon may be deflated, or left partially inflated. Leaving the angioplasty balloon partially inflated reduces the amount of radioactive liquid that must be used to fill the treatment balloon by occupying space within the IRT treatment balloon. Because of the self-attenuation of the radioactive liquid itself, most of the radioactivity originates at the surface of the treatment balloon. Accordingly, the surface radiation is not reduced substantially as a result of the center being filled with an inert material.
According to another embodiment of the present invention, a proximal and distal blocking balloon are also provided to contain the radioactive fluid in the target area in the event of a total failure of all containment systems.
According to another embodiment of the present invention, where a very low profile is required to access small blood vessels, the catheter comprises an inner angioplasty balloon and an outer balloon, however, the outer balloon inflation lumen is eliminated, thereby converting the outer balloon to a containment membrane. The IRT procedure is then carried out by filling the angioplasty balloon itself with the radioactive liquid after the angioplasty procedure has been performed. The containment membrane contains the radioactive liquid in the unlikely event that the angioplasty balloon, which previously withstood angioplasty pressures, ruptures under the more moderate IRT pressure.